The invention relates to a method for preparing pregnane derivatives and to certain intermediate esters useful therein.
For about ten years, 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione, produced by microbiological side chain degradation of sterols, have increasingly been utilized commercially as starting materials for the partial synthesis of pharmacologically effective steroids. As a consequence, the side chain buildup of androstane derivatives to form pregnane derivatives, which had even prior to this time been the object of intensive research activity (see, for example, J. Fried and J. A. Edwards: Organic Reactions in Steroid Chemistry, van Nostrand Reinhold Comp., New York, II: 127-236 [1976]), has increasingly gained in importance. Thus, 17.alpha.-ethynyl-17.beta.-nitrooxy steroids (prepared by ethynylation of 17-oxo steroids and esterification of the resultant 17.alpha.-ethynyl-17.beta.-hydroxy steroids with nitric acid in acetic anhydride) have been successfully converted into 17.beta.-acetyl-17.alpha.-formyl steroids (Chem. Ber. 111: 3086-3096 [1978]). These compounds are convertible, by means of known methods, into pregnane derivatives of general Formula I below, the further conversion of which into pharmacologically active steroids is well known. For example all of the compounds of Formula I can be converted using conventional methods into pharmacologically active steroids, for example, hydrocortisone, cortisone, 6.alpha.-methylhydrocortisone, prednisolone, 6.alpha.-methylprednisolone, D-homoprednisolone, 9-chloroprednisolone, esters of these compounds, etc. For example, the 9,11-saturated compounds can be 11.beta.-hydroxylated using microorganisms such as Curvularia lunata, etc. (See, e.g., W. Charney, H. L. Herzog, Microbial Transformations of Steroids, Academic Press, New York, etc., 1967); or to the 9,11-unsaturated compounds, HO-Cl or HO-Br can be added and, optionally, bromine cleaved. (See, e.g., GB No. 1,594,852; GB No. 2,089,809; GB No. 2,105,339; and U.S. patent applications Ser. No. 554,418 filed on Nov. 22, 1983; and Ser. No. 711,138 on Mar. 13, 1985.)